In the forthcoming year we plan to continue the study of the interaction of various ligands with three enzymes with which we have been working: papain, chymotrypsin, dihydrofolate reductase. With papain and chymotrypsin we are using correlation analysis to map the region around the active site to better understand how hydrolases work. With dihydrofolate reductase we are studying enzymes from a variety of sources: bacterial, normal mammalian, and tumor in order to find ways of selectively inhibiting enzymes. This will be of value in the design of better antibacterial agents. We hope that differences between normal mammalian enzyme and tumor enzyme can be found. Such differences could serve as points of departure in synthesis of better antitumor agents.